Submissions for variant NM_004370.6(COL12A1):c.9083G>A (p.Arg3028His)

gnomAD frequency: 0.00484  dbSNP: rs41266761

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000248918	SCV000310292	likely benign	not specified		criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000488209	SCV000575485	likely benign	not provided	2024-11-01	criteria provided, single submitter	clinical testing	COL12A1: BS2
Labcorp Genetics (formerly Invitae), Labcorp	RCV001082633	SCV000656213	benign	Ullrich congenital muscular dystrophy 2; Bethlem myopathy 2	2025-02-03	criteria provided, single submitter	clinical testing
Mendelics	RCV000987739	SCV001137179	likely benign	Ullrich congenital muscular dystrophy 2	2019-05-28	criteria provided, single submitter	clinical testing
GeneDx	RCV000488209	SCV001899412	benign	not provided	2020-09-14	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000248918	SCV002069829	likely benign	not specified	2020-04-29	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002519921	SCV003683191	uncertain significance	Inborn genetic diseases	2021-07-14	criteria provided, single submitter	clinical testing	The c.9083G>A (p.R3028H) alteration is located in exon 65 (coding exon 64) of the COL12A1 gene. This alteration results from a G to A substitution at nucleotide position 9083, causing the arginine (R) at amino acid position 3028 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000248918	SCV005884139	benign	not specified	2024-12-10	criteria provided, single submitter	clinical testing	Variant summary: COL12A1 c.9083G>A (p.Arg3028His) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0041 in 244726 control chromosomes, predominantly at a frequency of 0.007 within the Non-Finnish European subpopulation in the gnomAD database, including 8 homozygotes. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 2-fold of the estimated maximal expected allele frequency for a pathogenic variant in COL12A1 causing Ullrich congenital muscular dystrophy 2 phenotype (0.0035). To our knowledge, no occurrence of c.9083G>A in individuals affected with Ullrich congenital muscular dystrophy 2 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 259356). Based on the evidence outlined above, the variant was classified as benign.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000488209	SCV001799935	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000248918	SCV001807280	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000488209	SCV001919133	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000488209	SCV001975919	likely benign	not provided		no assertion criteria provided	clinical testing